Baxendale IR, Hayward JJ, Ley SV, Tranmer GK. Pharmaceutical strategy and innovation: an academics perspective. ChemMedChem. 2007;2(6):768–88. https://doi.org/10.1002/cmdc.200700008.

Article  CAS  PubMed  Google Scholar 

Nosengo N. New tricks for old drugs. Nature. 2016;534(7607):314–6. https://doi.org/10.1038/534314a.

Article  PubMed  Google Scholar 

Waring MJ, Arrowsmith J, Leach AR, Leeson PD, Mandrell S, Owen RM, et al. An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nat Rev Drug Discov. 2015;14(7):475–86. https://doi.org/10.1038/nrd4609.

Article  CAS  PubMed  Google Scholar 

Brimson JM, Brimson S, Chomchoei C, Tencomnao T. Using sigma-ligands as part of a multi-receptor approach to target diseases of the brain. Expert Opin Ther Targets. 2020;24(10):1009–28. https://doi.org/10.1080/14728222.2020.1805435.

Article  CAS  PubMed  Google Scholar 

Malar DS, Thitilertdecha P, Ruckvongacheep KS, Brimson S, Tencomnao T, Brimson JM. Targeting sigma receptors for the treatment of neurodegenerative and neurodevelopmental disorders. CNS Drugs. 2023;37(5):399–440. https://doi.org/10.1007/s40263-023-01007-6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brimson JM, Prasanth MI, Malar DS, Brimson S, Thitilertdecha P, Tencomnao T. Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: the possible role of the sigma-1 receptor and autophagy. Expert Opin Ther Targets. 2021;25(6):435–49. https://doi.org/10.1080/14728222.2021.1952987.

Article  CAS  PubMed  Google Scholar 

Prasanth MI, Wannigama DL, Reiersen AM, Thitilertdecha P, Prasansuklab A, Tencomnao T, et al. A systematic review and meta-analysis, investigating dose and time of fluvoxamine treatment efficacy for COVID-19 clinical deterioration, death, and long-COVID complications. Sci Rep. 2024;14(1):13462. https://doi.org/10.1038/s41598-024-64260-9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chomchoei C, Brimson JM, Brimson S. Repurposing fluoxetine to treat lymphocytic leukemia: apoptosis induction, sigma-1 receptor upregulation, inhibition of IL-2 cytokine production, and autophagy induction. Expert Opin Ther Targets. 2022;26(12):1087–97. https://doi.org/10.1080/14728222.2022.2166829.

Article  CAS  PubMed  Google Scholar 

Fallica AN, Ciaffaglione V, Modica MN, Pittalà V, Salerno L, Amata E, et al. Structure-activity relationships of mixed σ(1)R/σ(2)R ligands with antiproliferative and anticancer effects. Bioorg Med Chem. 2022;73:117032. https://doi.org/10.1016/j.bmc.2022.117032.

Article  CAS  PubMed  Google Scholar 

Oyer HM, Sanders CM, Kim FJ. Small-molecule modulators of sigma1 and sigma2/TMEM97 in the context of cancer: foundational concepts and emerging themes. Front Pharmacol. 2019;10:1141. https://doi.org/10.3389/fphar.2019.01141.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pontisso I, Combettes L. Role of sigma-1 receptor in calcium modulation: possible involvement in cancer. Genes. 2021. https://doi.org/10.3390/genes12020139.

Article  PubMed  PubMed Central  Google Scholar 

Hellewell SB, Bowen WD. A sigma-like binding site in rat pheochromocytoma (PC12) cells: decreased affinity for (+)-benzomorphans and lower molecular weight suggest a different sigma receptor form from that of guinea pig brain. Brain Res. 1990;527(2):244–53. https://doi.org/10.1016/0006-8993(90)91143-5.

Article  CAS  PubMed  Google Scholar 

Quirion R, Bowen WD, Itzhak Y, Junien JL, Musacchio J, Rothman RB, et al. A proposal for the classification of sigma binding sites. Trends Pharmacol Sci. 1992;13:85–6. https://doi.org/10.1016/0165-6147(92)90030-a.

Article  CAS  PubMed  Google Scholar 

Hayashi T, Su T-p. Intracellular dynamics of σ-1 receptors (σ1 binding sites) in NG108-15 cells. J Pharmacol Exp Ther. 2003;306(2):726–33. https://doi.org/10.1124/jpet.103.051292.

Article  CAS  PubMed  Google Scholar 

Cormaci G, Mori T, Hayashi T, Su T-p. Protein kinase A activation down-regulates, whereas extracellular signal-regulated kinase activation up-regulates sigma-1 receptors in B-104 cells: implication for neuroplasticity. J Pharmacol Exp Ther. 2007;320(1):202–10. https://doi.org/10.1124/jpet.106.108415.

Article  CAS  PubMed  Google Scholar 

Tsai S-y, Hayashi T, Harvey BK, Wang Y, Wu WW, Shen R-f, et al. Sigma-1 receptors regulate hippocampal dendritic spine formation via a free radical-sensitive mechanism involving Rac1 GTP pathway. Proc Natl Acad Sci U S A. 2009;106(52):22468–73. https://doi.org/10.1073/pnas.0909089106.

Article  PubMed  PubMed Central  Google Scholar 

Wu Z, Bowen WD. Role of sigma-1 receptor C-terminal segment in inositol 1,4,5-trisphosphate receptor activation. J Biol Chem. 2008;283(42):28198–215. https://doi.org/10.1074/jbc.M802099200.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aydar E, Palmer CP, Klyachko VA, Jackson MB. The sigma receptor as a ligand-regulated auxiliary potassium channel subunit. Neuron. 2002;34(3):399–410. https://doi.org/10.1016/s0896-6273(02)00677-3.

Article  CAS  PubMed  Google Scholar 

Natsvlishvili N, Goguadze N, Zhuravliova E, Mikeladze D. Sigma-1 receptor directly interacts with Rac1-GTPase in the brain mitochondria. BMC Biochem. 2015;16:11. https://doi.org/10.1186/s12858-015-0040-y.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brimson JM, Brown CA, Safrany ST. Antagonists show GTP-sensitive high-affinity binding to the sigma-1 receptor. Br J Pharmacol. 2011;164:772–80. https://doi.org/10.1111/j.1476-5381.2011.01417.x.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Su T-p, Hayashi T, Maurice T, Buch S, Ruoho AE. The sigma-1 receptor chaperone as an inter-organelle signaling modulator. Trends Pharmacol Sci. 2010;31(12):557–66. https://doi.org/10.1016/j.tips.2010.08.007.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sánchez-blázquez P, Rodríguez-muñoz M, Herrero-labrador R. The calcium-sensitive sigma-1 receptor prevents cannabinoids from provoking glutamate NMDA receptor hypofunction: implications in antinociception and psychotic diseases. Int J Neurosychopharmacol. 2014;17:1943–55. https://doi.org/10.1017/S1461145714000029.

Article  CAS  Google Scholar 

Ola MS, Moore P, El-Sherbeny A, Roon P, Agarwal N, Sarthy VP, et al. Expression pattern of sigma receptor 1 mRNA and protein in mammalian retina. Mol Brain Res. 2001;95(1–2):86–95. https://doi.org/10.1016/s0169-328x(01)00249-2.

Article  CAS  PubMed  Google Scholar 

Vilner BJ, John CS, Bowen WD. Sigma-1 and sigma-2 receptors are expressed in a wide variety of human and rodent tumor cell lines. Cancer Res. 1995;55(2):408–13.

CAS  PubMed  Google Scholar 

Pan L, Pasternak DA, Xu J, Xu M, Lu Z, Pasternak GW, et al. Isolation and characterization of alternatively spliced variants of the mouse sigma1 receptor gene, Sigmar1. PLoS One. 2017;12(3):e0174694. https://doi.org/10.1371/journal.pone.0174694.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schmidt HR, Zheng S, Gurpinar E, Koehl A, Manglik A, Kruse AC. Crystal structure of the human σ1 receptor. Nature. 2016;532:527–30. https://doi.org/10.1038/nature17391.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pal A, Hajipour AR, Fontanilla D, Ramachandran S, Chu UB, Mavlyutov T, et al. Identification of regions of the σ-1 receptor ligand binding site using a novel photoprobe. Mol Pharmacol. 2007;72(4):921–33. https://doi.org/10.1124/mol.107.038307.

Article